Hyperthermia, 41-44 degrees C, has been shown to potentiate the cellucidal effects of x-radiation. The combination of local hyperthermia and x-radiation is now being used in therapeutic programs for the treatment of a variety of malignancies. At the present time there is no data to indicate whether hyperthermia will alter the carcinogenic potential of ionizing radiation. 24 groups of mice will be exposed to either single or multiple (6 fractions) exposures of x-radiation to the leg. One half of the animals will also have the irradiated leg made hyperthermic for 45 minutes immediately following the x-radiation. Temperature of 37 degrees, 39 degrees, 41 degrees, or 43 degrees C will be used. The incidence, time of onset and the histological identity of the tumors developing at the treated site will be determined. Tumor growth rate and the presence of malignancies in other tissues will be observed. The acute and late skin reactions will also be measured to determine whether a moderate degree of hyperthermia may accelerate the repair of radiation damage rather than potentiate it. Preliminary observations by the PI indicate that the local x-radiaton followed by moderate hyperthermia (39 or 40 degrees C) significantly increase the risk of radiation induced tumors.